STRling: a k-mer counting approach that detects short tandem repeat expansions at known and novel loci

Harriet Dashnow; Brent S. Pedersen; Laurel Hiatt; Joe Brown; Sarah J. Beecroft; Gianina Ravenscroft; Amy J. LaCroix; Phillipa Lamont; Richard H. Roxburgh; Miriam J. Rodrigues; Mark Davis; Heather C. Mefford; Nigel G. Laing; Aaron R. Quinlan

doi:10.1186/s13059-022-02826-4

STRling: a k-mer counting approach that detects short tandem repeat expansions at known and novel loci

Harriet Dashnow, Brent S. Pedersen, Laurel Hiatt, Joe Brown, Sarah J. Beecroft, Gianina Ravenscroft, Amy J. LaCroix, Phillipa Lamont, Richard H. Roxburgh, Miriam J. Rodrigues, Mark Davis, Heather C. Mefford, Nigel G. Laing, Aaron R. Quinlan

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

Abstract

Expansions of short tandem repeats (STRs) cause many rare diseases. Expansion detection is challenging with short-read DNA sequencing data since supporting reads are often mapped incorrectly. Detection is particularly difficult for “novel” STRs, which include new motifs at known loci or STRs absent from the reference genome. We developed STRling to efficiently count k-mers to recover informative reads and call expansions at known and novel STR loci. STRling is sensitive to known STR disease loci, has a low false discovery rate, and resolves novel STR expansions to base-pair position accuracy. It is fast, scalable, open-source, and available at: github.com/quinlan-lab/STRling.

Original language	English
Article number	257
Number of pages	20
Journal	Genome Biology
Volume	23
Issue number	1
DOIs	https://doi.org/10.1186/s13059-022-02826-4
Publication status	Published - Dec 2022

Access to Document

10.1186/s13059-022-02826-4Licence: CC BY

Cite this

Dashnow, H., Pedersen, B. S., Hiatt, L., Brown, J., Beecroft, S. J., Ravenscroft, G., LaCroix, A. J., Lamont, P., Roxburgh, R. H., Rodrigues, M. J., Davis, M., Mefford, H. C., Laing, N. G., & Quinlan, A. R. (2022). STRling: a k-mer counting approach that detects short tandem repeat expansions at known and novel loci. Genome Biology, 23(1), Article 257. https://doi.org/10.1186/s13059-022-02826-4

@article{743ece37ef77446b99d083ee16a62107,

title = "STRling: a k-mer counting approach that detects short tandem repeat expansions at known and novel loci",

abstract = "Expansions of short tandem repeats (STRs) cause many rare diseases. Expansion detection is challenging with short-read DNA sequencing data since supporting reads are often mapped incorrectly. Detection is particularly difficult for “novel” STRs, which include new motifs at known loci or STRs absent from the reference genome. We developed STRling to efficiently count k-mers to recover informative reads and call expansions at known and novel STR loci. STRling is sensitive to known STR disease loci, has a low false discovery rate, and resolves novel STR expansions to base-pair position accuracy. It is fast, scalable, open-source, and available at: github.com/quinlan-lab/STRling.",

author = "Harriet Dashnow and Pedersen, {Brent S.} and Laurel Hiatt and Joe Brown and Beecroft, {Sarah J.} and Gianina Ravenscroft and LaCroix, {Amy J.} and Phillipa Lamont and Roxburgh, {Richard H.} and Rodrigues, {Miriam J.} and Mark Davis and Mefford, {Heather C.} and Laing, {Nigel G.} and Quinlan, {Aaron R.}",

note = "Funding Information: Support for this work was provided by the National Institutes of Health, National Heart, Lung, and Blood Institute, through BioData Catalyst program award 1OT3HL142479-01, 1OT3HL142478-01, 1OT3HL142481-01, 1OT3HL142480-01, 1OT3HL147154 to HD and NIH awards R01HG010757 and R01GM124355 to ARQ. GR is supported by the Australian NHMRC (Investigator Grant, APP2007769). NGL is supported by NHMRC Principal Research Fellowship APP1117510. This work is also supported by the MRFF Genomics Health Futures Mission Grant 2007681 (GR and NGL). Any opinions expressed in this document are those of the authors and do not necessarily reflect the views of NHLBI, individual BioData Catalyst Consortium members, or affiliated organizations and institutions. The computational resources used were partially funded by the NIH Shared Instrumentation Grant 1S10OD021644-01A1. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1186/s13059-022-02826-4",

language = "English",

volume = "23",

journal = "Genome Biology",

issn = "1474-7596",

publisher = "BioMed Central",

number = "1",

}

TY - JOUR

T1 - STRling

T2 - a k-mer counting approach that detects short tandem repeat expansions at known and novel loci

AU - Dashnow, Harriet

AU - Pedersen, Brent S.

AU - Hiatt, Laurel

AU - Brown, Joe

AU - Beecroft, Sarah J.

AU - Ravenscroft, Gianina

AU - LaCroix, Amy J.

AU - Lamont, Phillipa

AU - Roxburgh, Richard H.

AU - Rodrigues, Miriam J.

AU - Davis, Mark

AU - Mefford, Heather C.

AU - Laing, Nigel G.

AU - Quinlan, Aaron R.

N1 - Funding Information: Support for this work was provided by the National Institutes of Health, National Heart, Lung, and Blood Institute, through BioData Catalyst program award 1OT3HL142479-01, 1OT3HL142478-01, 1OT3HL142481-01, 1OT3HL142480-01, 1OT3HL147154 to HD and NIH awards R01HG010757 and R01GM124355 to ARQ. GR is supported by the Australian NHMRC (Investigator Grant, APP2007769). NGL is supported by NHMRC Principal Research Fellowship APP1117510. This work is also supported by the MRFF Genomics Health Futures Mission Grant 2007681 (GR and NGL). Any opinions expressed in this document are those of the authors and do not necessarily reflect the views of NHLBI, individual BioData Catalyst Consortium members, or affiliated organizations and institutions. The computational resources used were partially funded by the NIH Shared Instrumentation Grant 1S10OD021644-01A1. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - Expansions of short tandem repeats (STRs) cause many rare diseases. Expansion detection is challenging with short-read DNA sequencing data since supporting reads are often mapped incorrectly. Detection is particularly difficult for “novel” STRs, which include new motifs at known loci or STRs absent from the reference genome. We developed STRling to efficiently count k-mers to recover informative reads and call expansions at known and novel STR loci. STRling is sensitive to known STR disease loci, has a low false discovery rate, and resolves novel STR expansions to base-pair position accuracy. It is fast, scalable, open-source, and available at: github.com/quinlan-lab/STRling.

AB - Expansions of short tandem repeats (STRs) cause many rare diseases. Expansion detection is challenging with short-read DNA sequencing data since supporting reads are often mapped incorrectly. Detection is particularly difficult for “novel” STRs, which include new motifs at known loci or STRs absent from the reference genome. We developed STRling to efficiently count k-mers to recover informative reads and call expansions at known and novel STR loci. STRling is sensitive to known STR disease loci, has a low false discovery rate, and resolves novel STR expansions to base-pair position accuracy. It is fast, scalable, open-source, and available at: github.com/quinlan-lab/STRling.

UR - http://www.scopus.com/inward/record.url?scp=85144182477&partnerID=8YFLogxK

U2 - 10.1186/s13059-022-02826-4

DO - 10.1186/s13059-022-02826-4

M3 - Article

C2 - 36517892

AN - SCOPUS:85144182477

SN - 1474-7596

VL - 23

JO - Genome Biology

JF - Genome Biology

IS - 1

M1 - 257

ER -

STRling: a k-mer counting approach that detects short tandem repeat expansions at known and novel loci

Abstract

Access to Document

Other files and links

Fingerprint

Improving outcomes for individuals and families affected by genetic disease

Cite this

STRling: a k-mer counting approach that detects short tandem repeat expansions at known and novel loci

Abstract

Access to Document

Other files and links

Fingerprint

Projects

Improving outcomes for individuals and families affected by genetic disease

Cite this